Sex differences in the metabolic effects of diet-induced obesity vary by age of onset

Sex differences in the effect of diet-induced obesity (DIO) have been reported in juvenile mice. However, thorough side by side comparisons of the effects of DIO in males and females at different ages of onset have yet to be examined. We hypothesized that aged females would lose their protection, relative to males, from the effects of DIO. We examined the effect of DIO on body weight and glucose tolerance in juvenile, young adult, and middle-aged male and female mice. Our data show DIO in juvenile mice causes a greater increase in body weight and greater impairment in glucose tolerance in males than females. However, if the diet is initiated in young adult mice, these sex differences are absent. Further, if the diet is initiated in middle-aged mice, the sex difference is reversed, and females gain more weight and have greater impairment in glucose tolerance than males. Our data show that sex differences in the effect of DIO vary by age of onset; thus highlighting the importance of both age and sex as biological variables in DIO research.